Optically active alcohols have been widely used as a starting material or an intermediate for synthesis of fine chemicals, such as pharmaceuticals, agricultural chemicals, and liquid crystalline materials, and various compounds have recently been developed with the increasing demand therefor. For example, there are many useful optically active alcohols containing a phenyl group, such as 1-phenyl-1-ethanol, 1-phenyl-1-pentanol, and 1-(p-chlorophenyl)-1-ethanol. These optically active alcohols are required to have not only high chemical purity but high optical purity in order to exhibit sufficient functions therefrom.
Known purification techniques, such as solvent extraction, fractionation, recrystallization, simple distillation, azeotropic distillation, molecular distillation, and column chromatography, have been utilized for increasing chemical purity of optically active alcohols. On the other hand, increase in optical purity can effectively be achieved by optical resolution of a racemic alcohol using an enzyme (e.g., lipase, lipoprotein lipase, esterase and protease) to recover an optically active enantiomer(s). That is, it is difficult to separate an enantiomer from a racemic alcohol through ordinary chemical reactions accompanied by high temperatures, whereas reactions using an enzyme enables discrimination of enantiomers. Hence, production of optically active alcohols making use of the enzymatic reactions has been studied extensively.
Processes so far proposed for resolving a racemic alcohol using an enzyme to obtain an optically active alcohol include (i) hydrolysis of an ester of a racemic alcohol (see JP-A-1-137996 and JP-A-1-257484, the term "JP-A" as used herein means an "unexamined published Japanese patent application"), (ii) interesterification between a racemic alcohol and a triglyceride (see JP-A-62-166898, and JP-B-6-34752, the term "JP-B" as used herein means an "examined Japanese patent publication"), and (iii) interesterification between an ester of a racemic alcohol and an alcohol (see JP-A-63-173597).
Process (i) entails use of a large quantity of water. Where it is applied to a racemic alcohol ester having high affinity to water, such as a lower 2-alkanol, in an attempt to obtain an optically active alcohol with high purity (inclusive of chemical purity and optical purity, hereunder the same applies), the reaction product must be purified by complicated and expensive means, such as extraction or fractionation using a large amount of a solvent having selective dissolving power for a desired product and/or azeotropic distillation, molecular distillation or preparative liquid chromatography. Moreover, the enzyme tends to be inactivated because of the aqueous system and by-production of, for example, a carboxylic acid. If the enzyme is used in a powder form, it is practically impossible to recover and reuse the enzyme.
According to processes (ii) and (iii), on the other hand, the reaction system has only a trace water content and by-produces no substance causing inactivation of the enzyme so that an operation for extracting and separating a desired compound from an aqueous system as needed in process (i) is not necessary and the enzyme can be recovered and reused. However, in using lipase, for example, since a conventional reaction temperature ranges from about 20.degree. to 70.degree. C. at the broadest and preferably from 20.degree. to 50.degree. C., applicable starting materials are limited to those which are liquid in this temperature range or otherwise must be used in a dissolved state in an organic solvent. In addition, racemic alcohols, particularly those having a substituent of large molecular size, such as a phenyl group, exhibit low reactivity due to steric hindrance of their chemical structure and therefore require a very long time of from several days or even longer for completion of the reaction at such low reaction temperatures as above mentioned.
Where interesterification of process (ii) or (iii) is carried out according to conventional techniques and in the absence of a solvent, starting materials (i.e., racemic alcohols, racemic alcohol esters, triglycerides, alcohols, etc.) which can be used in practice are required to have a melting point approximately equal to or lower than the enzymatic reaction temperature. Accordingly, it is unavoidable to select starting materials having physical properties similar to each other, such as a melting point, a boiling point or solubility in a solvent. Where the reaction of process (iii) is carried out in an organic solvent system (cf. JP-A-63-173597), the alcohol, one of the starting materials, contains 1 to 10 carbon atoms and has a similar melting point to the other starting material, i.e., a racemic alcohol ester. If starting materials having similar physical properties are used, purification means taking advantage of a difference in physical properties among various components can hardly be adopted for efficiently separating and recovering a desired optically active alcohol with increased chemical and optical purity from the interesterification reaction product in which the starting compounds and the reaction product generally provide a complicated equilibrium composition. Therefore, processes (ii) and (iii) as well as process (i) should have a problem that complicated and expensive purification means are necessary.